Non-steroidal anti-inflammatory drugs and endometrial cancer risk in the VITamins and Lifestyle (VITAL) cohort

Objective: Chronic inflammation may be an important factor in the initiation and promotion of endometrial cancer. Use of non-steroidal anti-inflammatory drugs (NSAIDs), however, has been inconsistently associated with endometrial cancer risk. Methods: 22,268 female residents of western Washington State, ages 50-76, completed a baseline questionnaire in 2000-2002 and reported on their use of individual NSAIDs over the past 10 years. Use was categorized as none, low (< 4 days/week or < 4 years), and high (≥ 4 days/week and ≥ 4 years). Over 9 years of follow-up, 262 incident invasive endometrial cancers were identified. Multivariable proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results: Relative to non-use, high use of aspirin was inversely associated with endometrial cancer risk (HR 0.64, 95% CI: 0.41-1.01; P trend = 0.03). Findings were stronger for regular-strength than low-dose aspirin. High use of non-aspirin NSAIDs (HR 1.15, 95% CI: 0.68-1.95), including ibuprofen (HR 1.29, 95% CI: 0.73-2.28), and naproxen (HR 1.08, 95% CI: 0.39-2.95) was not associated with risk. In subgroup analyses, findings for aspirin were strongest for cancers of endometrioid histology and were restricted to non-smokers. Conclusions: This study provides additional evidence that use of aspirin, but not non-aspirin NSAIDs, may reduce the risk of endometrial cancer, especially in estrogen-mediated cases; however additional prospective studies with high-quality measurement of NSAID use are needed. Aspirin should continue to be examined as a potential agent for cancer chemoprevention.